Biliary atresia reflects total or partial agenesis of the biliary tree and usually affects extrahepatic, rather than intrahepatic, bile ducts. Extrahepatic biliary atresia (EHBA) is a heterogeneous, rare disease, which is fatal if untreated. The incidence of EHBA varies considerably in various geographic areas but is estimated to affect one in 18,000 live births each year in the United States alone. EHBA results from the discontinuous or failed development of bile ducts to the gut. Without the ducts, bile detergents begin to degrade the bile brush border of the bile capillary epithelium and these materials leak to the venous sinusoids of the liver, ultimately connecting to the systemic circulation. In most cases, biliary atresia develops several weeks after birth, probably following inflammation and scarring of the bile ducts. It is rarely found in still-borns or in the immediate neonatal period. The etiology of the inflammatory response is often unknown.
Affected children may appear normal at birth and are recognized due to progressive obstructive jaundice at three to six weeks of age. This course reflects the pathologic changes within the bile ducts in biliary atresia, namely, a dynamic evolution from a patent biliary tract at birth to progressive ductal obstruction and biliary cirrhosis.
Appropriate evaluations can usually exclude other specific causes of neonatal obstructive jaundice, such as specific infections, galactosemia and cystic fibrosis, but differentiation between neonatal hepatitis and EHBA may be difficult due to the histologic similarities between their resultant pathologic changes. Early diagnosis is essential, because successful biliary decompression becomes increasingly unlikely with increasing patient age. Without surgical evaluation and reconstruction, prolonged biliary hypertension causes permanent and progressive liver damage that may lead to metabolic complications, infection, sclerotizing cholangitis and cirrhosis, and may end in terminal liver insufficiency. Therefore, in the absence of findings positively securing an alternative diagnosis, biliary atresia must be excluded.
Direct and total bilirubin values, liver enzymes, alkaline phosphatase and serum levels of bile acids usually rule out infections and metabolic disorders but will not clearly distinguish EHBA from neonatal hepatitis. Imaging studies involving radiographic evaluation or ultrasound examination of the gall bladder and of extrahepatic bile ducts may be helpful but are nonspecific. The placement of a nasoduodenal tube and collection of a 24 hour sample of duodenal fluid by gravity drainage may reveal the presence of bile (bilirubin can not be measured); bile excretion is strong evidence against a diagnosis of complete biliary atresia. Such a procedure, however, is invasive. Another invasive procedure is percutaneous liver biopsy which requires interpretation by an experienced physician.
If the diagnosis is still uncertain in excluding EHBA, a laparotomy must be performed before two months of age, because infants with EHBA will develop irreversible biliary cirrhosis if the operation is deferred. Atretic bile ducts can be successfully reanastomosed in 5 to 10% of infants. EHBA is a progressive disease, and if corrective surgery is not performed prior to about eight weeks of age, there is only about a 25% chance of survival. If the corrective procedure is not performed or fails, a liver transplant becomes necessary. It is therefore critical to detect EHBA between 2-8 weeks of age.
Upon diagnosis, EHBA is surgically treated. A few patients (.+-.15%) with EHBA have anatomic lesions which are amenable to an anastomotic procedure providing direct suture of the gut mucosa to that of a proximally patent extrahepatic biliary tree. Most patients (.+-.85%) are not candidates for direct anastomosis. These patients had a hopeless prognosis and short life span prior to the surgical approach by Kasai of hepatoportoenterostomy which involves the direct surgical mucosa-to-mucosa anastomosis of the porta hepatis to the bowel. (Karrer et al., Surg. Clin. North Am. 70:1403-18 (1990) and Tagge et al., Ann. Surg. 214:590-8 (1991)). In cases where permanent liver damage is present, the treatment of choice is liver transplantation (Ryckman et al., Semin. Liver Dis. 7:134-54 (1987); Wall W. J., Can. Med. Assoc. J. 139:21-8 (1988); and Esquivel et al., J. Pediatr. 111:1039-45 (1987)).
With early diagnostic screening procedures, the number of unnecessary, early transplantations might be reduced by timely surgical intervention. In countries and areas where liver transplantation is not available, early diagnosis followed by surgical correction is the only chance of survival for patients with EHBA.
About 1/3 of all newborns appear jaundiced at birth. About 1/10 of these remain jaundiced after approximately 10 days. These newborns would be candidates for an EHBA diagnostic. A screening program was recently advised for EHBA in the United Kingdom. The usefulness of the screening program, however, has been sharply debated due to the lack of a simple and specific detection technology (Logan et al., Lancet 342:256 (1993)). Therefore, a simple and accurate non invasive test to evaluate EHBA would be invaluable to early diagnosis and treatment.